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N Chung

Publications and source records attributed to N Chung.

60 records · Page 4Linked to original sources

Formation and metabolism of 5(10)-estrene-3 beta,17 beta-diol, a novel 19-norandrogen produced by porcine granulosa cells from C19 aromatizable androgens.

The biosynthesis of non-aromatic 19-norsteroids has been studied using primary cultures of porcine granulosa cells. Formation of 5(10)-estrene-3 beta,17 beta-diol, a novel 19-norsteroid, from androstenedione and 19-hydroxyandrostenedione by porcine granulosa cells is reported for the first time. The structure was deduced from (i) comparison of its elution times on C18 reverse phase HPLC with authentic 5(10)-estrene-3 beta,17 beta-diol (ii) identification with 5(10)-estrene-3 beta,17 beta-diol-diacetate after acetylation (iii) oxidation/acid catalysed isomerization to 19-norandrostenedione. Serum or serum plus FSH significantly stimulated (seven fold increase) formation of 5(10)-estrene-3 beta,17 beta-diol from androstenedione and 19-hydroxyandrostenedione. Formation of 5(10)-estrene-3 beta,17 beta-diol from both substrates was significantly (p less than 0.01) reduced by the aromatase inhibitors 4-hydroxyandrostenedione (15 microM) and aminoglutethimide phosphate (10(-4)M). These results suggest that 5(10)-estrene-3 beta,17 beta-diol (and 19-norandrostenedione) may be formed by enzymes similar to the aromatase complex required for estradiol-17 beta biosynthesis. 5(10)-Estrene-3 beta,17 beta-diol is converted by granulosa cells to four metabolites. 19-Norandrostenedione was identified by crystallization to constant specific activity; 19-nortestosterone is a minor product. Production of 19-norandrostenedione and 19-nortestosterone indicates that granulosa cells possess the enzymes necessary for the transformation of 5(10)-estrene-3 beta,17 beta-diol and other 3-hydroxy-5(10)-estrenes to 19-nor-4-ene-3-ketosteroids. The formation of 5(10)-estrene-3 beta,17 beta-diol and 19-norandrostenedione as substantial metabolites of androstenedione suggest a physiological role for these 19-norsteroids in ovarian follicular development.

Acetylation↗

LV chamber extraction from 3-D CT images--accuracy and precision.

Measurement of left ventricular (LV) chamber volume and shape from three-dimensional (3-D) CT images, generated by the fast X-ray CT scanner known as the dynamic spatial reconstructor, has previously been done using manual slice-image editing. To reduce the exorbitant operator analysis time and operator-dependent measurement variations of manual slice-image editing, we have devised a semiautomatic method for LV-chamber extraction. The method draws upon a minimum requirement for selective manual slice-image editing and mostly makes use of automatic image-analysis operations. Detailed validation results over a wide range of hemodynamic and image-analysis conditions show that the measurements of the semiautomatic method strongly correlate with those made via manual slice-image editing and exhibit a lower intertrial variability. Further, the method reduces operator interaction time by nearly an order of magnitude over that of manual slice-image editing, but provides more detailed 3-D structural definition.

Animals↗

Measurement of left ventricular dp/dt by simultaneous Doppler echocardiography and cardiac catheterization.

Left ventricular dp/dt is a useful isovolumic index for evaluating acute directional changes in myocardial contractility. To test the hypothesis that Doppler echocardiography can measure left ventricular dp/dt by using the mitral regurgitation velocity curve, 14 patients with at least a mild degree of mitral regurgitation (four with coronary artery disease, four with valvular heart disease, four with dilated cardiomyopathy, one with carcinoid, and one with mitral valve prosthesis) were studied by continuous-wave Doppler echocardiography. Simultaneously, left ventricular pressure was measured with a manometer-tipped catheter to generate actual dp/dt. Curves of left ventricular pressure and mitral regurgitant Doppler-derived velocities of three cardiac cycles were digitized at 1-msec intervals. The rate of Doppler-derived velocity increase was converted to a rate of pressure increase by using the modified Bernoulli equation. Mean dp/dt during various time intervals of the mitral regurgitation velocity envelope (1 to 2 m/sec, 2 to 3 m/sec, and 1 to 3 m/sec) corresponding to left ventricular-left atrial pressure differences of 12, 20, and 32 mm Hg, respectively, were calculated. Doppler-derived left ventricular dp/dt (y) correlated with catheter-derived left ventricular dp/dt (x) as follows: at the 1 to 2 m/sec interval, y (mm Hg/sec) = 0.84x + 137, r = 0.91, SEE = 90; at the 2 to 3 m/sec interval, y = 1.1x - 89, r = 0.96, SEE = 80; and at the 1 to 3 m/sec interval, y = 1.1x + 23, r = 0.98, SEE = 50.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm.

BACKGROUND: It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (123I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of 123I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. METHODS AND RESULTS: Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2+/-12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n = 18) comprised subjects with a positive provocative test result, and group 2 (n = 8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using 123I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal 123I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of 123I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of 123I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. CONCLUSION: 123I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in 123I-MIBG SPECT.

3-Iodobenzylguanidine↗

Induction of humoral immune response and protective immunity in chickens against Salmonella enteritidis after a single dose of killed bacterium-loaded microspheres.

Formalin-inactivated Salmonella enteritidis phage type 4 strain 119/95 (SE) was encapsulated in biodegradable poly (DL-lactide co-glycolic acid) PLGA; (65:35) microspheres by a modified water-in-oil-in-water (w/o/w) double-emulsion solvent extraction/evaporation technique. These SE-loaded microspheres (SE-MS) were porous and spherical in shape with diameters of 0.4-10 microm and 20-80 microm in two preparations. SE-MS were subsequently used to vaccinate specific-pathogen-free chickens in a single dose in order to investigate the potency of a single-dose vaccination in inducing immune responses and protective immunity. In Experiment 1, 4-wk-old chickens that were vaccinated intramuscularly with 20-80-microm SE-MS generated long lasting (over 6 mo) and persistently high serum anti-SE immunoglobulin (Ig)G antibody response. In Experiment 2, 2-wk-old chickens were vaccinated orally with 0.4-10-microm or intramuscularly with 20-80-microm SE-MS and challenged with 10(9) colony-forming units of homologous SE strain at 6 wk postvaccination. When challenged intramuscularly, one each of the orally vaccinated (n = 10) and the intramuscularly vaccinated birds (n = 10) showed clinical signs and death, whereas all of the nonvaccinated control birds (n = 12) were sick and 11 of them were killed. When challenge was via oral route, 26.1% of cloacal swabs and 24.0% of organs (liver, spleen, and cecum) collected from orally vaccinated birds (n = 35) were positive for SE, comparable to 27.9% of feces and 18.7% of organs from the intramuscularly vaccinated birds (n = 35). These figures were significantly lower than those for nonvaccinated birds (n = 30) from which 59.3% of feces and 44.0% of organs tested SE positive (P < 0.05). The humoral immune response was also determined after vaccination with a single dose. The intramuscular vaccination elicited higher serum IgG response than oral administration, but the latter elicited a significant intestinal mucosal IgA antibody response. This is the first evidence that chickens vaccinated with killed SE-loaded PLGA microspheres, intramuscularly and orally in a single dose, developed systematic and local immune responses, thereby conferring protective immunity.

Administration, Oral↗

Effects of acute changes in canine LV-chamber volume and shape on accuracy of impedance catheter estimates of LV-chamber volume.

The accuracy with which a multiple-electrode impedance catheter (IC) tracks instantaneous global, in-situ left ventricular (LV) volumes was tested in 13 anesthetized dogs scanned in the Dynamic Spatial Reconstructor (DSR), a fast volumetric computed tomographic (CT) scanner. All dogs were scanned during control conditions and during an acute hemodynamic intervention. Hypertonic saline calibrations were performed for the IC prior to each DSR scan. In six of the dogs the IC-derived LV end-diastolic volume (Y) correlated with the DSR-derived global LV end-diastolic volume (X) as follows: end-diastolic volume, Y = 1.01X - 9.9, r = 0.812. The IC-derived LV end-diastolic volume, under control conditions, correlated with the DSR-derived truncated (i.e., that region of the LV chamber between the proximal and distal electrodes of the IC catheter) LV end-diastolic volume, Y = 1.00X + 17.4, r = 0.803. Under reduced preload the relation was Y = 1.3X - 15.26, r = 0.911. The segmental volume (between adjacent sensing electrodes on the IC) at the basal portion of the LV correlated poorly (Y = 1.88X + 3.3, r = 0.459 etc.), but correlated better at mid- and more apical LV levels (Y = 0.97X + 2.7, r = 0.762). Correlations between segmental stroke volumes were similar at basal (Y = 1.31X + 1.60, r = 0.815) and mid- and more apical levels (Y = 1.42X + 0.11, r = 0.763). Stroke volume during acute ischemia (two dogs) was Y = 1.33X - 1.41, r = 0.717; during acutely decreased preload (four dogs) it was Y = 1.24X - 2.88, r = 0.572). Thus, the IC tracks the changes in LV-chamber volume throughout a cardiac cycle quite well under a variety of conditions, but accuracy deteriorates as the shape of the LV chamber changes in response to changes in hemodynamic loading or local myocardial ischemia.

Animals↗